FoxP3 reporter mice expressing green fluorescence protein (GFP) have been used as a very convenient tool to investigate the impact of regulatory T (Treg) cells on pathogenesis in autoimmune diseases. Here, we found that GFP-FoxP3+ knock-in (KI) mice showed alterations in the production of anti-nuclear autoantibodies (ANAs) and nephritis with different extent, depending on the presence or absence of lupus susceptibility gene locus 1 (Sle1) and KI method: contrasting with B6.Sle1.fGFP-FoxP3 mice, expressing GFP via N-terminal insertion, B6.Sle1.iGFP-FoxP3, expressing GFP via bicistronic internal ribosome entry site-driven promotion, exhibited significantly lower penetrance of serum ANA, comparing to control B6.Sle1 mice. Moreover, B6.Sle1.GFP-FoxP3+ mice reduced the Sle1-induced splenomegaly and B-cell expansion independently of the KI method employed, mainly by reducing the numbers of transitional 1 (T1) B cells and CD21-CD23- B cells, including plasmablasts and plasma cells. The absolute numbers of both splenic CD4+ T cells and Treg cells from B6.Sle1.GFP-FoxP3 KI mice were significantly reduced but their proportion was not changed, compared to B6.Sle1 mice. Although the glomerular basement membranes were thickened in both B6.Sle1 and B6.Sle1.iGFP-FoxP3 mice, they were thinner in B6.Sle1.fGFP-FoxP3 mice. The latter mice expressed more nephrophilic autoantibodies and deposited more complement component 3 in glomeruli compared to B6.iGFP-FoxP3 mice. FoxP3+ Treg cells may modulate B-cell tolerance in lupus-prone B6.Sle1 mice, presumably by modulating pathogenic, nephrophilic autoantibody production and nephritis.

中文翻译：

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GFP-FoxP3 +调节性T细胞对狼疮标志的影响因遗传背景和GFP敲入类型而异。

表达绿色荧光蛋白（GFP）的FoxP3报告基因小鼠已被用作研究调节性T（Treg）细胞对自身免疫性疾病发病机理的非常方便的工具。在这里，我们发现GFP-FoxP3 +敲入（KI）小鼠显示抗核自身抗体（ANAs）和肾炎的产生程度不同，这取决于狼疮易感基因基因座1（Sle1）和KI方法：与B6.Sle1.fGFP-FoxP3小鼠通过N端插入表达GFP，B6.Sle1.iGFP-FoxP3小鼠通过双顺反子内部核糖体进入位点驱动的促进表达GFP相比，血清ANA的渗透率显着降低，与对照B6.Sle1小鼠相比。此外，B6.Sle1。GFP-FoxP3 +小鼠独立于所采用的KI方法，减少了Sle1诱导的脾肿大和B细胞扩增，主要是通过减少了过渡1（T1）B细胞和CD21-CD23- B细胞（包括浆母细胞和浆细胞）的数量。与B6.Sle1小鼠相比，B6.Sle1.GFP-FoxP3 KI小鼠的脾脏CD4 + T细胞和Treg细胞的绝对数量均明显减少，但比例没有改变。尽管在B6.Sle1和B6.Sle1.iGFP-FoxP3小鼠中肾小球基底膜均增厚，但在B6.Sle1.fGFP-FoxP3小鼠中它们更薄。与B6.iGFP-FoxP3小鼠相比，后者的小鼠表达更多的亲肾自身抗体，并在肾小球中沉积了更多的补体成分3。FoxP3 + Treg细胞可能调节易患狼疮B6.Sle1小鼠的B细胞耐受性，可能是通过调节致病性，